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东印度(2014-2016 年)G3 轮状病毒的爆发和传播:全基因组分析显示 Wa 样基因组构成内的异质性。

Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.

机构信息

Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases (ICMR-NICED), Kolkata 700010, India.

Infectious diseases and Beliaghata General (ID & BG) Hospital, Beliaghata, Kolkata 700010, India.

出版信息

Infect Genet Evol. 2018 Sep;63:158-174. doi: 10.1016/j.meegid.2018.05.026. Epub 2018 May 26.

DOI:10.1016/j.meegid.2018.05.026
PMID:29842980
Abstract

Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis. During diarrheal disease surveillance at Kolkata, India (2014-2016), a shift in circulating RVA strains from G1P[8] to G3P[8] was seen. Stool samples from children (n = 3048) with acute gastroenteritis were tested of which 38.7% were RVA positive. G1 was the predominant strain (65.3%) in 2014-2015 whereas in late 2015 and 2016, G3 became the preponderant strain (44.6%). In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains. The analyses revealed intergenogroup reassortment in G3P[4] strains (among Wa and DS-1-like genogroup) whereas G3P[8] strains were authentic Wa-like. Phylogenetic analysis revealed Kolkata G3 strains as polymorphic and thus they formed two sub-clusters due to antigenic differences in their VP7 protein. One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation. Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains. The study is important as efficiency of rotavirus vaccine depends on the circulating heterogeneous genotype constellations. Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.

摘要

轮状病毒 A 组(RVA)是引起儿童肠胃炎的主要原因之一,其新毒株的出现和主要流行基因型的转变是其特征。在印度加尔各答进行的腹泻病监测(2014-2016 年)中,发现循环 RVA 株从 G1P[8]转变为 G3P[8]。对 3048 例急性肠胃炎患儿的粪便样本进行了检测,其中 38.7%为 RVA 阳性。2014-2015 年,G1 是主要流行株(65.3%),而在 2015 年末和 2016 年,G3 成为主要流行株(44.6%)。在过去的十年中,该地区未观察到 G3 株,我们对代表株进行了全基因组测序,以深入了解这些循环人类 G3 株的出现和遗传特征。分析表明,G3P[4]株(Wa 和 DS-1 样基因型组之间)发生了基因型间重组,而 G3P[8]株是真正的 Wa 样株。系统进化分析显示,加尔各答 G3 株具有多态性,因此由于其 VP7 蛋白的抗原差异,它们形成了两个亚群。其中一个亚群在 87 位氨基酸处具有野生型苏氨酸,而另一个亚群具有异亮氨酸突变。VP7 糖蛋白 283 位氨基酸上存在额外的 N-连接糖基化位点,表明 RotaTeq 疫苗 VP7(G3)上的主要中和表位与目前流行的 G3 株不同。该研究很重要,因为轮状病毒疫苗的效率取决于循环的异质基因型组合。因此,在印度等流行地区,连续监测循环 RVA 株对于接种前和接种后监测新重组基因型的出现以及评估疫苗效果非常重要。

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